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Liwei Liu, Jihong Yao, Zhenlu Li, Guo Zu, Dongcheng Feng, Yang Li, Wasim Qasim, Su Zhang, Tong Li, Huizhi Zeng, Xiaofeng Tian
Impairment in gut barrier function induced by intestinal ischemia/reperfusion (I/R) injury is associated with high morbidity and mortality. Intestinal barrier function requires the tight coordination of epithelial migration, proliferation and differentiation. We previously observed that nuclear receptor-related protein 1 (nurr1)-mediated proliferative pathway was impaired in intestinal I/R injury. Here, we aimed to assess the effect of nurr1 on intestinal barrier function and to evaluate microRNA (miRNA)-nurr1-mediated restoration of intestinal barrier function in intestinal I/R injury...
March 14, 2018: Cell Death & Disease
Roberto De Gregorio, Salvatore Pulcrano, Claudia De Sanctis, Floriana Volpicelli, Ezia Guatteo, Lars von Oerthel, Emanuele Claudio Latagliata, Roberta Esposito, Rosa Maria Piscitelli, Carla Perrone-Capano, Valerio Costa, Dario Greco, Stefano Puglisi-Allegra, Marten P Smidt, Umberto di Porzio, Massimiliano Caiazzo, Nicola Biagio Mercuri, Meng Li, Gian Carlo Bellenchi
The differentiation of dopaminergic neurons requires concerted action of morphogens and transcription factors acting in a precise and well-defined time window. Very little is known about the potential role of microRNA in these events. By performing a microRNA-mRNA paired microarray screening, we identified miR-34b/c among the most upregulated microRNAs during dopaminergic differentiation. Interestingly, miR-34b/c modulates Wnt1 expression, promotes cell cycle exit, and induces dopaminergic differentiation. When combined with transcription factors ASCL1 and NURR1, miR-34b/c doubled the yield of transdifferentiated fibroblasts into dopaminergic neurons...
March 2, 2018: Stem Cell Reports
Han Gao, Lianrong Dou, Liang Shan, Yan Sun, Wentao Li
Neural stem cells (NSCs) are important cellular sources of transplantation therapies for Parkinson's disease. This study aimed to determine the effects of extracts of radix astragali on the proliferation and differentiation into dopamine (DA) neurons in NSCs. NSCs were dealt with astragaloside IV (ASI), astragalus polysaccharide (APS), and astraisoflavan (ASF), the main active ingredients of radix astragali. First, the results from cell-count kit-8 (CCK-8) assay showed that ASI, ASF, and APS had positive effects on the proliferation of NSCs...
February 23, 2018: Neuroreport
Chan Li, Genghong Tu, Chaohua Luo, Youli Guo, Miao Fang, Chen Zhu, Hancheng Li, Jinying Ou, Yuting Zhou, Wei Liu, Ken Kin Lam Yung, Zhixian Mo
In the past few years, ketamine, a noncompetitive NMDA antagonist, has been widely abused worldwide as a new type of synthetic drug, severely affecting the physical and mental health of ketamine abusers. Previous studies have suggested that rhynchophylline can alleviate drug abuse and reverse the conditioned place preference caused by the abuse. MicroRNAs (miRNAs) are important factors regulating gene expression and are involved in the drug addiction process. The hippocampus is a critical area in the brain involved in causing drug addiction...
February 21, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Xiaoxiang Chen, Yuan Qian, Xiangpeng Wang, Zhiwei Tang, Jiaotian Xu, Hai Lin, Zhiyong Yang, Xiaobin Song, Di Lu, Jiazhi Guo, Ligong Bian, Yu Li, Lei Zhou, Xingli Deng
INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life...
February 15, 2018: CNS Neuroscience & Therapeutics
Shireen A Hedya, Marwa M Safar, Ashraf K Bahgat
Nuclear receptor related 1 (Nurr1) orphan receptor has emerged as a promising contender in ameliorating Parkinson's disease; thus, finding a suitable activator of Nurr1 receptor is an attracting target for treating PD. Cilostazol, a phosphodiesterase-3 inhibitor, recently showed a favorable neuroprotective activity in multiple devastating central disorders, yet the possible antiparkinsonian activity of the drug has not been fully elucidated. Thus, the aim of this study is to explore the neuroprotective effect of cilostazol in rotenone-induced PD model in rats...
February 10, 2018: Molecular Neurobiology
Oumei Cheng, Xiaoyan Tian, Ying Luo, Shaoshan Mai, Yang Yang, Shengnan Kuang, Qi Chen, Jie Ma, Beibei Chen, Rong Li, Lu Yang, Huan Li, Congli Hu, Jiahua Zhang, Zhihao Chen, Yuke Li, Hui Xia, Ying Xu, Junqing Yang
Dopaminergic (DA) neurons derived from bone marrow derived mesenchymal stem cells (BMSCs) maybe a valuable source for cell replacement therapy in Parkinson disease. Recent studies showed that new functions of LXR and their ligands have been proposed to prevent PD in the adult nervous system. The present study was designed to observe the effect of liver X receptors (LXR) agonist on differentiation of rat BMSCs into DA neurons. Expressions of the neuronal markers (Tuj1 and Nestin), the specific marker of DA neurons (tyrosine hydroxylase, TH), LXR α and LXR β were measured by immunocytochemical assay and TH/Tuj1 positive cells were determined by quantitative cell count analyses...
January 2, 2018: Oncotarget
Meng Wang, Lilah Fones, John W Cave
Tyrosine hydroxylase (Th) encodes the rate-limiting enzyme in catecholamine biosynthesis, and the regulation of its transcription is critical for the specification and maintenance of catecholaminergic neuron phenotypes. For many genes, regulatory genomic DNA sequences that are upstream of the proximal promoter control expression levels as well as region-specific expression patterns. The regulatory architecture of the genomic DNA upstream of the Th proximal promoter, however, is poorly understood. In this study, we examined the 11 kb upstream nucleotide sequence of Th from nine mammalian species and identified five highly conserved regions...
February 5, 2018: Molecular Neurobiology
Amitis Karrys, Islam Rady, Roxane-Cherille N Chamcheu, Marya S Sabir, Sanchita Mallick, Jean Christopher Chamcheu, Peter W Jurutka, Mark R Haussler, G Kerr Whitfield
Treatment with 1,25-dihydroxyvitamin D₃ (1,25D) improves psoriasis symptoms, possibly by inducing the expression of late cornified envelope (LCE)3 genes involved in skin repair. In psoriasis patients, the majority of whom harbor genomic deletion of LCE3B and LCE3C (LCE3C_LCE3B-del), we propose that certain dietary analogues of 1,25D activate the expression of residual LCE3A/LCE3D/LCE3E genes to compensate for the loss of LCE3B/LCE3C in the deletant genotype. Herein, human keratinocytes (HEKn) homozygous for LCE3C_LCE3B-del were treated with docosahexaenoic acid (DHA) and curcumin, two low-affinity, nutrient ligands for the vitamin D receptor (VDR)...
February 4, 2018: Nutrients
Qingqing Liu, Qi Qin, Hongxue Sun, Di Zhong, Ran An, Yushuang Tian, Hongping Chen, Jing Jin, Haining Wang, Guozhong Li
AIMS: The aim of the study is to evaluate the neuroprotective effects of olfactory ensheathing cells (OECs) with the overexpression of nuclear receptor-related factor 1 (Nurr1) and neurogenin 2 (Ngn2) in experimental models of Parkinson's disease (PD) and to elucidate the potential mechanism underlying the neuroprotective effects of OECs-Nurr1-Ngn2. MATERIALS AND METHODS: In vitro study, OECs-Nurr1-Ngn2 conditioned medium (CM) was added to MPP+-treated PC12 cells for 24h, and then the viability of PC12 cells, oxidative stress and apoptosis were detected...
December 29, 2017: Life Sciences
Peijian Yue, Lin Gao, Xuejing Wang, Xuebing Ding, Junfang Teng
The purpose of this study was to investigate ultrasound-triggered effects of the glial cell line-derived neurotrophic factor (GDNF) + nuclear receptor-related factor 1 (Nurr1)-polyethylene glycol (PEG)ylated liposomes-coupled microbubbles (PLs-GDNF + Nurr1-MBs) on behavioral impairment and neuron loss in a rat model of Parkinson's disease (PD). The unloaded PEGylated liposomes-coupled microbubbles (PLs-MBs) were characterized for zeta potential, particle size, and concentration. 6-hydroxydopamine (6-OHDA) was used to establish the PD rat model...
December 14, 2017: Journal of Cellular Biochemistry
Robert Yl Tsai
Most of the adult CNS lacks regenerative activity in terms of both neuron birth and neurite outgrowth. While this regeneration-unfriendly environment of the adult CNS may preserve the existing neuronal circuitry that takes years to develop in higher organisms, it also poses a major obstacle for CNS repair later in life. In this issue of the JCI, Song et al. report on their development of a strategy that uses region-specific and molecularly engineered astrocytes to turn an unfavorable brain environment into a favorable one for engrafted neural stem/progenitor cells (NSC/NPCs)...
January 2, 2018: Journal of Clinical Investigation
Jae-Jin Song, Sang-Min Oh, Oh-Chan Kwon, Noviana Wulansari, Hyun-Seob Lee, Mi-Yoon Chang, Eunsoo Lee, Woong Sun, Sang-Eun Lee, Sunghoe Chang, Heeyoung An, C Justin Lee, Sang-Hun Lee
Transplantation of neural progenitor cells (NPCs) is a potential therapy for treating neurodegenerative disorders, but this approach has faced many challenges and limited success, primarily because of inhospitable host brain environments that interfere with enriched neuron engraftment and function. Astrocytes play neurotrophic roles in the developing and adult brain, making them potential candidates for helping with modification of hostile brain environments. In this study, we examined whether astrocytic function could be utilized to overcome the current limitations of cell-based therapies in a murine model of Parkinson's disease (PD) that is characterized by dopamine (DA) neuron degeneration in the midbrain...
January 2, 2018: Journal of Clinical Investigation
Xuemei Xie, Li Peng, Jin Zhu, Yang Zhou, Lingyu Li, Yanlin Chen, Shanshan Yu, Yong Zhao
Nurr1 is a member of the nuclear receptor 4 family of orphan nuclear receptors that is decreased in inflammatory responses and leads to neurons death in Parkinson's disease. Abnormal expression of Nurr1 have been attributed to various signaling pathways, but little is known about microRNAs (miRNAs) regulation of Nurr1 in ischemia/reperfusion injury. To investigate the post transcriptional regulatory networks of Nurr1, we used a miRNA screening approach and identified miR-145-5p as a putative regulator of Nurr1...
2017: Frontiers in Molecular Neuroscience
Mohammad Hasan Soheilifar, Arash Javeri, Hossein Amini, Masoumeh Fakhr Taha
Several studies have demonstrated the differentiation of human adipose tissue-derived stem cells (hADSCs) to neuronal and glial phenotypes, but directing the fate of these cells toward dopaminergic neurons has not been frequently reported. The aim of the present study was to investigate dopaminergic specification of hADSCs in vitro. ADSCs were isolated from subcutaneous abdominal adipose tissue and were characterized. For dopaminergic differentiation, a cocktail of sonic hedgehog, fibroblast growth factor 8, basic fibroblast growth factor and brain-derived neurotrophic factor were used under a low serum condition...
December 5, 2017: Rejuvenation Research
Baek-Soo Han, Nguyen Van Minh, Ha-Young Choi, Jung-Su Byun, Won-Gon Kim
The methanol extract of the roots and stems of Daphne genkwa and its constituents yuanhuacin (1) and genkwanine N were previously reported to have Nurr1 activating effects and neuroprotective effects in an animal model of Parkinson's disease (PD). In this study, four more daphnane-type diterpenes (acutilonine F (2), wikstroemia factor M1 (3), yuanhuadine (5), and yuanhuatine (6)) and two phorbol-type diterpenes (prostratin Q (4) and 12-O-n-deca-2,4,6-trienoyl-phorbol-(13)-acetate (7)) were isolated as Nurr1 activating compounds from the D...
2017: Biological & Pharmaceutical Bulletin
Simone Mesman, Marten P Smidt
The basic helix-loop-helix (bHLH) protein family has previously been shown to be involved in the development of mesodiencephalic dopaminergic (mdDA) neurons in the murine midbrain. Specifically, Ngn2 and Mash1 are known to have a role in the specification of neural progenitors in the ventricular zone (VZ) of the midbrain towards an mdDA neuronal cell-fate. Furthermore, other members of the bHLH protein family, the E-box factors, are expressed in the developing midbrain and are thought to have a role in neuronal differentiation...
2017: Frontiers in Molecular Neuroscience
Jing Ma, Cui Huang, Kun Ma, Yan-Ping Wu, Bai-Xiang Li, Yan Sun
Paraquat (PQ) and maneb (MB) are widely used herbicides. Wingless (Wnt) proteins serve a role in the development and differentiation of dopaminergic neurons. Previous studies demonstrated that combined exposure to PQ and MB damages dopaminergic neurons in the midbrain. Effects of PQ and MB exposure on midbrain Wnt proteins have also been previously reported. In the present study, from the 5th day of gestation to weaning of the offspring, pregnant Sprague‑Dawley rats were administrated saline, or PQ and MB at two different doses: high, 15 mg/kg body weight PQ + 45 mg/kg body weight MB; or low, 10 mg/kg body weight PQ + 30 mg/kg body weight MB...
December 2017: Molecular Medicine Reports
Kazuko Takahashi-Niki, Takeshi Niki, Sanae M M Iguchi-Ariga, Hiroyoshi Ariga
DJ-1 is an oncogene and also a causative gene for familial Parkinson's disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. DJ-1-regulating transcription factors and their modified proteins are the androgen receptor and its regulatory proteins, p53; polypyrimidine tract-binding protein-associated splicing factor (PSF); Keap1, an inhibitor for nuclear factor erythroid2-related factor 2 (Nrf2); sterol regulatory element-binding protein (SREBP); Ras-responsive element-binding protein (RREB1); signal transducer and activator of transcription 1 (STAT1); and Nurr1...
2017: Advances in Experimental Medicine and Biology
Luis Alberto Pereira, Roberto Munita, Marcela Paz González, María Estela Andrés
The development of mesencephalic dopamine neurons and their survival later in life requires the continuous presence of the transcription factor Nurr1 (NR4A2). Nurr1 belongs to the nuclear receptors superfamily. However, it is an orphan member that does not require a ligand to regulate the transcription of its target genes. Therefore, controlling the expression of Nurr1 is an important manner to control its function. Several reports have shown that microRNAs (miRNAs) regulate Nurr1 expression. However, Nurr1 has several splicing variants, posing the question what variants are subjected to miRNA regulation...
2017: PloS One
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